@article {Nelson151,
author = {Nelson, M E and Albuquerque, E X},
title = {9-Aminoacridines act at a site different from that for Mg2+ in blockade of the N-methyl-D-aspartate receptor channel.},
volume = {46},
number = {1},
pages = {151--160},
year = {1994},
publisher = {American Society for Pharmacology and Experimental Therapeutics},
abstract = {The effects of alkylene bis-9,9{\textquoteright}-aminoacridines and 1,2,3,4-tetrahydro-9-aminoacridine (THA) were studied on single-channel currents activated by N-methyl-D-aspartate (NMDA) in outside-out patches from cultured rat hippocampal neurons. These compounds reduced the channel open times with concentration and voltage dependence, which was consistent with an open-channel blockade mechanism of action. In nominally Mg(2+)-free solutions, the forward blocking rate constants for 1,2-propane-bis-9,9{\textquoteright}-aminoacridine, 1,4-butane-9,9{\textquoteright}-aminoacridine, and THA were 1.1 x 10(8), 1.4 x 10(8), and 3.5 x 10(7) M-1 sec-1, respectively, at a holding potential of -80 mV. The unblocking rate constants for the bis-9-aminoacridines were similar and in the range of 7 sec-1, whereas THA had an unblocking rate constant of approximately 6.2 x 10(3) sec-1. In the presence of Mg2+ (approximately 5 microM), the predictions of the model for open-channel blockade by the 9-aminoacridines were invalid, because the relationships between the channel lifetimes and 9-aminoacridine concentrations were not linear. The effects of Mg2+ (approximately 0-50 microM) on the open-channel blockade of the NMDA receptor by the 9-aminoacridines were evaluated further by measuring the burst times in the presence of 1,2-propane-bis-9,9{\textquoteright}-aminoacridine (5 microM). The results suggested that the interactions of 9-aminoacridines and Mg2+ with the ion channel of the NMDA receptor were not mutually exclusive. Simultaneous occupancy of the NMDA receptor ion channel by Mg2+ and a channel-blocking organic cation could be a common mechanism of channel blockade for this receptor under physiological conditions.},
issn = {0026-895X},
URL = {http://molpharm.aspetjournals.org/content/46/1/151},
eprint = {http://molpharm.aspetjournals.org/content/46/1/151.full.pdf},
journal = {Molecular Pharmacology}
}